DB, the receptor for leptin

Abstract

The present invention relates to identification of a receptor for a satiety factor, which is involved in body weight homeostasis. Mutations in this receptor are associated with obese phenotypes. In particular, the present invention relates to identification and characterization of the receptor for leptin, including a naturally occurring soluble form of the receptor that is expected to modulate leptin activity, in particular to agonize leptin activity. The invention further relates to the nucleic acids encoding the receptor, and to methods for using the receptor, e.g., to identify leptin analogs, therapeutically, such as in gene therapy or in soluble form as an agonist or antagonist of leptin activity, or diagnostically.

1. An isolated leptin receptor (OB-R) polypeptide which is OB-Re (SEQ ID NO:10). 
     
     
       2. An isolated leptin receptor (OB-R) polypeptide of amino acids 28–805 of SEQ ID NO:10. 
     
     
       3. An isolated soluble leptin receptor which is selected from OB-Re (SEQ ID NO:10) and amino acids 28–805 of SEQ ID NO:10. 
     
     
       4. A pharmaceutical composition comprising a soluble leptin receptor according to  claim 3 , and a pharmaceutically acceptable carrier. 
     
     
       5. A body appearance improving cosmetic composition for modulating the body weight of an individual comprising a soluble leptin receptor of  claim 3 , and an acceptable carrier. 
     
     
       6. The isolated leptin receptor (OB-R) polypeptide of any of  claims 1 ,  2  or  3  which is a soluble receptor and which is encoded by a nucleic acid which is amplifiable in a polymerase chain reaction (PCR) with a PCR probe selected from group consisting of a probe for clone 7 (forward primer SEQ ID NO:42 and reverse primer SEQ ID NO:43), a probe for clone 11 (forward primer SEQ ID NO:44 and reverse primer SEQ ID NO:45), and both clone 7 and clone 11. 
     
     
       7. The isolated leptin receptor (OB-R) polypeptide of any of  claims 1 ,  2  or  3  which is a soluble receptor and which is encoded by a nucleic acid which is amplifiable in a PCR reaction with a PCR probe selected from the group consisting of a probe for clone S14 (forward primer SEQ ID NO:51 and reverse primer SEQ ID NO:52); and a probe for clone S3 (forward primer SEQ ID NO:53 and reverse primer SEQ ID NO:54).